Amy Hudson

Abstract Disclosure: M. Maher: None. R. McEvoy: None. V. Farnan: None. D.J. Tansey: None. S. McKenna: None. J. O'Connell: None. R. McQuillan: None. M. Griffin: None. J. Lyne: None. C. Magee: None. C. Traynor: None. A. Hudson: None. M.W. O'Reilly: None. A. Agha: None. M. Sherlock: None. C.M. Moran: None. Background: Amiodarone-induced thyrotoxicosis (AIT) is challenging to manage where conventional medical treatment fails. We report our experience using therapeutic plasma exchange (TPE) to prepare for salvage thyroidectomy. Clinical Cases: A 53-year-old man was diagnosed with AIT type 2 (FT4 45.3pmol/L, RR 12-22; TSH 0.02mU/L, RR 0.27-4.20) whilst on amiodarone, on a background of lamin A/C cardiomyopathy. He remained thyrotoxic despite carbimazole, prednisolone, iodine solution and cholestyramine. TFTs following 4 TPE sessions showed an improvement in TSH (0.03mU/L) and total T4 (129nmol/L, RR 63-151), despite rising FT4 (91.5pmol/L) and FT3 (12.56pmol/L, RR 2.43-6.01).A 47-year-old man was diagnosed with TRAb-negative AIT type 1 (FT4 51.2pmol/L, TSH 0.03mU/L) on a background of atrial fibrillation treated with amiodarone. He became progressively more thyrotoxic despite carbimazole, prednisolone, lithium and cholestyramine. Following 4 TPE sessions, TFTs demonstrated a reduction in FT4 (42.9pmol/L) and FT3 (10pmol/L, RR 3.1-6.8), along with normalisation of total T4 (155nmol/L, RR 66-181).A 56-year-old female was diagnosed with AIT type 2 (FT4 33.9pmol/L, TSH 0.02mU/L), whilst on amiodarone for ventricular fibrillation. She became rapidly and progressively more thyrotoxic despite carbimazole, prednisolone, iodine solution and cholestyramine (FT4 >100pmol/L). After 5 TPE sessions, TFTs showed a persistently elevated FT4 (>100pmol/L), FT3 (13.1pmol/L), and total T4 (318nmol/L). Lastly, a 65-year-old gentleman was diagnosed with AIT type 2 (FT4 >100pmol/L, FT3 18.4pmol/L, Total T4 >320nmol/L, TSH <0.01mU/L) on a background of atrial fibrillation that had been treated with amiodarone. FT3 showed a modest reduction (8.2pmol/L) following treatment with carbimazole and prednisolone; however, FT4 remained >100pmol/L. The patient developed acute decompensated heart failure and underwent TPE as a bridge to emergency thyroidectomy. Following 3 TPE sessions, TFTs demonstrated a reduction in FT4 (67.3pmol/L) and Total T4 (223nmol/L). All 4 patients underwent uneventful thyroidectomy and were subsequently rendered euthyroid with thyroxine. Heparin was administered during TPE in all cases. Conclusion: TPE is beneficial as a bridge to thyroidectomy in treatment-resistant AIT. Our cases demonstrate that the biochemical response is variable. Given the possibility for heparin to cause displacement of bound thyroid hormones, Total T4 may be a better biochemical indicator of response than free thyroid hormone(s) for patients on TPE. Presentation: 6/2/2024

Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the most common monogenic cause of kidney failure. While identifying genetic variants predicts disease progression, characterization of recently described ADPKD-like variants is limited. We explored disease progression and genetic spectrum of genetically-confirmed ADPKD families with PKD1 and non-PKD1 variants. In this observational study, we evaluated the clinical (ADPKD-related complications, estimated glomerular filtration rate (eGFR) decline, and progression to kidney failure), radiological (height-adjusted total kidney volume (ht-TKV)), and genetic characteristics of ADPKD families referred to the Irish Kidney Gene Project. Logistic regression and Kaplan–Meier analyses examined relationships between genetic variants and disease progression. Genomic sequencing was performed on 261 ADPKD families, and 75.8% (198/261 families, comprising 391 individuals) were identified to harbor pathogenic/likely pathogenic variants; 74.2% (147/198) PKD1 families and 23.2% (46/198) non-PKD1 families, which include PKD2 (n = 29 families), IFT140 variants (n = 4), ALG5, DNAJB11 and NEK8 (n = 3 each), ALG8 and ALG9 variants (n = 2 each). The remaining 2.6% (5/198) accounted for non-ADPKD variants. Compared to PKD1, non-PKD1 families were characterized by a milder phenotype; milder eGFR decline (− 1.4 mL/min/1.73m2/year vs. − 3.2; p < 0.001), smaller ht-TKV (449.7 mL/m vs. 1769; p 0.002) and a delayed progression towards kidney failure (73 vs. 52 years; HR: 0.12, p < 0.001 [95% CI: 0.07–0.19]). ADPKD-NEK8 heterozygotes demonstrated earlier progression to kidney failure (average age 8 vs. 49 years for PKD1; Bonferroni-corrected p 0.017). Non-PKD1 variants have heterogeneous phenotypic and genotypic attributes resulting in milder disease, although ADPKD-NEK8 is an important exception with early progression.